Maximal Ca2+-activated force elicited by tetanization of ferret papillary muscle and whole heart: Mechanism and characteristics of steady contractile activation in intact myocardium

E. Marban, H. Kusuoka, D. T. Yue

Research output: Contribution to journalArticlepeer-review

Abstract

Rapid (8-12 Hz) stimulation of intact heart muscle treated with ryanodine results in steady contractile activation known as tetanus, the amplitude of which can be graded by changing extracellular Ca2+ concentration ([Ca2+](o)). The mechanism of the sustained force generation was explored in ferret papillary muscles by measuring membrane potential and by determining the responsiveness of force and intracellular free Ca2+ concentration ([Ca2+](i), estimated with aequorin) to dihydropyridine Ca channel ligands. Membrane potential during tetani ranged from -25 to -60 mV, suggesting that fast or slow Ca channels, or Na-Ca exchange, might be mediating Ca2+ entry. Dihydropyridine effects indicated that slow Ca channels play a predominant role: The agonist Bay K 8644 (0.3-1 μM) increased force and aequorin luminescence, whereas the antagonist nitrendipine (1-30 μM) abolished the tetanus. Under conditions analogous to those in the papillary muscle experiments, tetani were produced in whole Langendorff-perfused ferret hearts following exposure to ryanodine. Contraction saturated as a function of [Ca2+](o) in both papillary muscles and whole hearts; i.e., as [Ca2+](o) was increased above 10 mM, no further increase in force or pressure generation occurred. In contrast, aequorin luminescence measured in the papillary muscles showed no such saturation. Thus, maximal Ca2+-activated force (or pressure) was achieved during tetani at [Ca2+](o) ≥ 10 mM. Calculations of wall stress during tetani in whole heart (15 mM [Ca2+](o)) agree well with direct measurements of maximal tension in papillary muscles (5.84 g/mm2 vs. 6.41 g/mm2, respectively). We conclude that maximal Ca2+-activated force (or pressure) can be produced during tetani at high [Ca2+](o) in either whole hearts or isolated papillary muscles following exposure to ryanodine.

Original languageEnglish (US)
Pages (from-to)262-269
Number of pages8
JournalCirculation research
Volume59
Issue number3
DOIs
StatePublished - 1986

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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